Ongoing Pregnancy Live Birth Rate Research Articles

The association of obesity with euploidy rates in women undergoing in vitro fertilization with preimplantation genetic testing.

The purpose of this study was to determine the impact of body mass index (BMI) on euploidy rates for in vitro fertilization (IVF) cycles with preimplantation genetic testing (PGT) utilizing primarily next-generation sequencing (NGS). This retrospective cohort study included women aged ≤ 45years who underwent IVF/PGT between September 2013 and September 2020 at a single university-affiliated fertility center. The primary outcome was euploidy rate. Secondary outcomes included peak serum estradiol (E2), number of oocytes retrieved, oocyte maturation rate, high-quality blastulation rate, clinical loss rate (CLR), clinical pregnancy rate (CPR), and ongoing pregnancy/live birth rate (OPR/LBR). The study included 1335 IVF cycles thatwere stratified according toBMI (normal, n = 648; overweight, n = 377; obese, n = 310). The obese group was significantly older with significantly lower baseline FSH, peak E2, high-quality blastulation rate, and number of embryos biopsied than the normal group. Overall euploidy rates were not significantly different between BMI groups (normal 36.4% ± 1.3; overweight 37.3% ± 1.8; obese 32.3% ± 1.8; p = 0.11), which persisted after controlling for covariates (p = 0.82) and after stratification of euploidy rate by age group and by number of oocytes retrieved per age group. There were no significant differences in CLR, CPR, and OPR/LBR across BMI groups. Despite a lower high quality blastulation rate with obesity, there is not a significant difference in euploidy rates across BMI groups in women undergoing IVF/PGT.

Combined Preimplantation Genetic Testing for Genetic Kidney Disease: Genetic Risk Identification, Assisted Reproductive Cycle, and Pregnancy Outcome Analysis.

BackgroundGenetic kidney disease is a major cause of morbidity and mortality in neonates and end-stage renal disease (ESRD) in children and adolescents. Genetic diagnosis provides key information for early identification of congenital kidney disease and reproductive risk counseling. Preimplantation genetic testing for monogenic disease (PGT-M) as a reproductive technology helps prospective parents to prevent passing on disease-causing mutations to their offspring.Materials and MethodsA retrospective cohort of couples counseled on PGT who had a risk to given birth to a child with genetic kidney disease or had a history of prenatal fetal kidney and urinary system development abnormalities from 2011 to 2021. Through a combination of simultaneously screening for aneuploidy and monogenic kidney disease, we achieved reproductive genetic intervention.ResultsA total of 64 couples counseled on PGT for monogenic kidney disease in a single reproductive center during the past 10 years, of whom 38 different genetic kidney diseases were identified. The most frequent indications for referral were autosomal recessive disease (54.7%), then autosomal dominant disease (29.7%), and X-linked disease (15.6%). Polycystic kidney disease was the most common diseases counted for 34.4%. After oocyte-retrieval in all of 64 females, a total of 339 embryos were diagnosed and 63 embryos were transferred in succession. Among 61 cycles of frozen-embryo transfer (FET), ongoing pregnancy/live birth rate (OP/LBR) reached 57.38%. The cumulative OP/LBR in our cohort for the 64 couples was 54.69%. In addition, we have carried out expanded carrier screening (ECS) in all the in vitro fertilization (IVF) couples performed PGT covering 7,311 individuals. The carrier frequency of the candidate genes for monogenic kidney diseases accounted for 12.19%.ConclusionOverall, the customization PGT-M plan in our IVF center is pivotal to decreasing the morbidity and implementing reproductive genetic intervention of genetic kidney disease.

Clinical error rates of next generation sequencing and array comparative genomic hybridization with single thawed euploid embryo transfer.

We investigated clinical error rates with single thawed euploid embryo transfer (STEET) diagnosed by next generation sequencing (NGS) and array comparative genomic hybridization (aCGH). A total of 1997 STEET cycles after IVF with preimplantation genetic testing for aneuploidy (PGT-A) from 2010 to 2017 were identified; 1151 STEET cycles utilized NGS, and 846 STEET cycles utilized aCGH. Any abortions, spontaneous or elective, in which products of conception (POCs) were collected were reviewed. Discrepancies between chorionic villus sampling, amniocentesis, or live birth results and PGT-A diagnosis were also included. Primary outcomes were clinical error rate per: ET, pregnancy with gestational sac, live birth, and spontaneous abortion with POCs available for analysis. Secondary outcomes included implantation rate (IR), spontaneous abortion rate (SABR), and ongoing pregnancy/live birth rate (OPR/LBR). The clinical error rates in the NGS cohort were: 0.7% per embryo, 1% per pregnancy with gestational sac, and 0.1% rate per OP/LB. The error rate per SAB with POCs was 13.3%. The IR was 69.1%, the OPR/LBR was 61.6%, and the spontaneous abortion rate was 10.2%. The clinical error rates in the aCGH cohort were: 1.3% per embryo, 2% per pregnancy with gestational sac, and 0.4% rate per OP/LB. The error rate per SAB with POCs was 23.3%. The IR was 63.8%, the OPR/LBR was 54.6%, and the SAB rate was 12.4%. Our findings demonstrate that, although NGS and aCGH are sensitive platforms for PGT-A, errors still occur. Appropriate patient counseling and routine prenatal screening are recommended for all patients undergoing IVF/PGT-A.

Why Do Euploid Embryos Fail to Implant? The Role of CD138 and Chronic Endometritis

The objective of this prospective cohort study was to investigate the relationship between chronic endometritis (CE) and its treatment on pregnancy outcomes in patients undergoing frozen embryo transfers (FETs) from in vitro fertilization (IVF) with preimplantation genetic testing (PGT) who had previously failed ≥ 1 euploid FET. The diagnosis of CE was made using CD138 as a marker. This study occurred at a single, high volume academic based fertility center. 305 patients were included with a history of ≥ 1 failed euploid transfers. 59 patients underwent endometrial biopsies (EMB) prior to subsequent FET (Tested), 246 patients did not undergo EMB prior to subsequent transfer (Untested). Patients in the Tested group had an EMB prior to subsequent FET, whereas the patients in the Untested group did not have an EMB prior to next FET. Patients tested and found positive for CE were treated with antibiotics and underwent test-of-cure (TOC) EMBs prior to next FET to assess for adequate treatment. Patients without CE on EMB proceeded to next FET without antibiotic treatment. Main outcome measures included positive Beta-hCG (βhCG) on cycle day 28, implantation rate (IR), and subsequent ongoing pregnancy/live birth rates (OPR/LBR). Our results showed that 51% of patients (30/59) were diagnosed with CE and treated with antibiotics (Tested, CE treated); negative TOC biopsies were obtained prior to next FET. 49% of patients (29/59) tested negative for CE (Tested, No CE) and were not treated prior to next FET. Tested patients without CE (CE treated and No CE) had significantly higher incidences of positive βhCG, IR and OPR/LBR than patients who were not tested. Those who were biopsied and treated for CE had significantly higher OPR/LBR compared to patients who were biopsied and negative for CE (80% vs. 55%). We conclude that CE is common, with a prevalence of 51% in patients who have failed euploid FETs. Testing for CE may provide a benefit to patients, assuring higher incidences for positive βhCG, implantation, and subsequent ongoing/live births. CE is a treatable condition warranting investigation in patients with poor pregnancy outcomes.

Endometrial scratching for infertile women undergoing a first embryo transfer: a systematic review and meta-analysis of published and unpublished data from randomized controlled trials

To investigate endometrial scratch injury (ESI) as an intervention to improve IVF outcome in women undergoing a first ET. Systematic review and meta-analysis. Not applicable. Infertile women undergoing a first fresh/frozen embryo transfer. We included published and unpublished data from randomized controlled trials in which the intervention group received ESI and controls received placebo or no intervention. Pooled results were expressed as relative risk (RR) with 95% confidence interval (CI). The review protocol was registered in PROSPERO to start the data extraction (CRD42018087786). Ongoing pregnancy/live birth rate (OPR/LBR), clinical pregnancy rate (CPR), multiple pregnancy rate (MPR), miscarriage rate (MR), and ectopic pregnancy rate (EPR). Seven studies were included (1,354 participants). We found a nonsignificant difference between groups in terms of OPR/LBR, CPR, MR, MPR, and EPR. Subgroup analysis found that ESI on the day of oocyte retrieval (achieved by a Novak curette) reduced OPR/LBR (RR 0.31, 95% CI 0.14-0.69) and CPR (RR 0.36, 95% CI 0.18-0.71), whereas ESI during the cycle preceding ET (performed through soft devices) had no effect on OPR/LBR and CPR. No difference in the impact of ESI was observed between fresh and frozen embryo transfer. Current evidence does not support performing ESI with the purpose of improving the success of a first ET attempt.

Pituitary block with gonadotrophin-releasing hormone antagonist during intrauterine insemination cycles: a systematic review and meta-analysis of randomised controlled trials.

Several randomised controlled trials (RCTs) have investigated the usefulness of pituitary block with gonadotrophin-releasing hormone (GnRH) antagonists during intrauterine insemination (IUI) cycles, with conflicting results. The aim of the present systematic review and meta-analysis of RCTs was to evaluate the effectiveness of GnRH antagonist administration as an intervention to improve the success of IUI cycles. Electronic databases (MEDLINE, Scopus, EMBASE, Sciencedirect) and clinical registers were searched from their inception until October 2017. Randomised controlled trials of infertile women undergoing one or more IUI stimulated cycles with GnRH antagonists compared with a control group. The primary outcomes were ongoing pregnancy/live birth rate (OPR/LBR) and clinical pregnancy rate (CPR). Pooled results were expressed as odds ratio (OR) or mean differences with 95% confidence interval (95% CI). Sources of heterogeneity were investigated through sensitivity and subgroups analysis. The body of evidence was rated using GRADE methodology. Publication bias was assessed with funnel plot, Begg's and Egger's tests. Fifteen RCTs were included (3253 IUI cycles, 2345 participants). No differences in OPR/LBR (OR 1.14, 95% CI 0.82-1.57, P = 0.44) and CPR (OR 1.28, 95% CI 0.97-1.69, P = 0.08) were found. Sensitivity and subgroup analyses did not provide statistical changes in pooled results. The body of evidence was rated as low (GRADE 2/4). No publication bias was detected. Pituitary block with GnRH antagonists does not improve OPR/LBR and CPR in women undergoing IUI cycles. Pituitary block with GnRH antagonists does not improve the success of IUI cycles.

Next generation sequencing for preimplantation genetic screening improves pregnancy outcomes compared with array comparative genomic hybridization in single thawed euploid embryo transfer cycles

To evaluate whether the use of next generation sequencing (NGS) for preimplantation genetic screening (PGS) in single thawed euploid embryo transfer (STEET) cycles improves pregnancy outcomes compared with array comparative genomic hybridization (aCGH). Retrospective cohort study. Single university-based fertility center. A total of 916 STEET cycles from January 2014 to December 2016 were identified. Cases included 548 STEET cycles using NGS for PGS and controls included 368 STEET cycles using aCGH for PGS. Patients having a STEET after undergoing IVF and PGS with either NGS or aCGH. Primary outcomes were implantation rate, ongoing pregnancy/live birth rate (OP/LBR), biochemical pregnancy rate (PR), and spontaneous abortion (SAB) rate. The implantation rate was significantly higher in the NGS group compared with the aCGH group (71.6% vs. 64.6%). The OP/LBR was also significantly higher in the NGS group (62% vs. 54.4%), and there were significantly more biochemical pregnancies in the aCGH group compared with the NGS group (15.1% vs. 8.7%). After adjustment for confounding variables with a multiple logistic regression analysis, OP/LBR remained significantly higher in the NGS group. The SAB rate was not significantly different in the NGS group compared with the aCGH group (12.4% vs. 12.7%). Preimplantation genetic screening using NGS significantly improves pregnancy outcomes versus PGS using aCGH in STEET cycles. Next-generation sequencing has the ability to identify and screen for embryos with reduced viability such as mosaic embryos and those with partial aneuploidies or triploidy. Pregnancy outcomes with NGS may be improved due to the exclusion of these abnormal embryos.

Preimplantation genetic screening (PGS) with next generation sequencing (NGS) achieves ongoing pregnancy with fewer transfers and total miscarriages compared to non-PGS cycles

To determine the cumulative ongoing pregnancy/live birth rates (OP/LBR) of PGS cycles with NGS compared to non-PGS cycles using an intention to treat analysis. Cohort Study All patients undergoing an oocyte retrieval for IVF or IVF/PGS with NGS and their subsequent frozen embryo transfer (FET) cycles at a single university-based fertility center were collected from 1/2014 through 7/2016. Embryo banking cycles, donor oocyte cycles, cycles utilizing PGS with array comparative genomic hybridization, and IVF cycles with no blastocyst stage embryos were excluded. Cumulative OP/LBRs were calculated per retrieval including up to 4 transfers and analyzed by age-group. IVF/PGS cycles with no euploid embryos available for transfer were included. Secondary outcomes included the number of embryos transferred per cycle, cumulative OP/LBR after the first embryo transfer (ET), and cumulative spontaneous abortion rate (SABR) per clinical pregnancy. Statistical analysis was performed using Fisher’s exact test with P<0.05 considered significant. 2547 cycles meeting inclusion criteria were identified. 844 retrievals and 525 FET cycles were performed in the PGS with NGS group. In the no PGS group, there were 953 retrievals and 225 FET cycles. 242 retrieval cycles did not form blastocysts and were excluded. The number of embryos transferred per cycle was significantly higher in the no PGS group than the PGS with NGS group (1.58±0.69 vs 1.01±0.11, p<0.001). Primary and secondary outcomes are summarized in the table. Per retrieval, there was no statistical difference in cumulative OP/LBR between groups. Pregnancy was achieved more often after the first transfer in women 38-40 years old. The cumulative OP/LBR per retrieved patient with embryos available for transfer was significantly higher for the PGS group over age 35. The cumulative SABR was significantly higher for ages 38-42yo in the no PGS group.Tabled 1Cumulative OP/LBR Per Retrieval (%) by agePGS with NGSNo PGSP- value<3562.6% (97/155)70.1% (169/241)0.1535-3750.3% (86/171)53.8% (78/145)0.6138-4042.4% (109/257)38% (62/163)0.4341-4217.9% (29/162)21.1% (15/71)0.68>427.1% (7/98)10.3% (8/78)0.64OP/LBR after 1st ET per Retrieval (%) by agePGS with NGSNo PGSP- value<3554.2% (84/155)47.3% (114/241)0.2235-3745.6% (78/171)40.7% (59/145)0.4438-4039.3% (101/257)29.4% (48/163)0.04941-4216% (26/162)18.3% (13/71)0.8>426.1% (6/98)9% (7/78)0.66Cumulative OP/LBR per retrieved patient with embryos available for transfer (%) by agePGS with NGSNo PGSP-value<3574.6% (97/130)70.1% (169/241)0.4335-3771.1% (86/121)53.8% (78/145)0.00638-4070.8% (109/154)38% (62/163)<0.00141-4267.4% (29/43)21.1% (15/71)<0.001>4246.7% (7/15)10.3% (8/78)0.004Cumulative SABR per clinical pregnancy (%) by agePGS with NGSno PGSP- value<3510.2% (11/108)14.5% (28/193)0.3735-3714.9% (15/101)20.4% (20/98)0.3638-4011.7% (14/120)28.6% (24/84)0.00441-4214.7% (5/34)46.4% (13/28)0.013>4212.5% (1/8)55.6% (10/18)0.1 Open table in a new tab Overall, cumulative OP/LBRs are similar in women undergoing IVF with or without PGS, but IVF cycles without PGS have significantly more embryos transferred per cycle. Retrievals utilizing PGS with NGS result in OP/LB with fewer embryo transfers in women 38-40 years old and fewer miscarriages in women ages 38-42.

Serum progesterone levels greater than 20ng/dl on day of embryo transfer are associated with lower live birth and higher pregnancy loss rates.

Progesterone (P4) is essential for support of the endometrium and implantation of an embryo in the normal menstrual cycle. In programed frozen embryo transfer cycles using exogenous P4 is necessary, as the endogenous production of P4 requires a functioning corpus luteum that is not present in programed cycles. To date, there is continuing debate about ideal serum estradiol and P4 values in frozen embryo transfer cycles. Patients underwent single euploid embryo frozen transfer cycles from 2010 to 2013 at a single large academic center. Patients using donor oocytes and patients with changes in progesterone dose during the cycles in question were excluded. All cycles were programed and intramuscular P4 was used exclusively. Only patients administering the same daily dose of P4 throughout the cycle were included (N = 213 patients). Main outcomes were ongoing pregnancy/live birth rates (OPR/LBR), clinical pregnancy rates (CPR), and spontaneous abortions/biochemical pregnancies. CPR was defined by the presence of a sac on 1st trimester ultrasound. Missed abortions were calculated per pregnancy with a sac. Receiver operator characteristic curves (ROC curves) and chi-squared tests were performed for statistical analysis. Two groups based on day 19 P4 levels were compared (group A, P4 < 20ng/ml; group B, P4 > 20ng/ml). OPR/LBRs were 65 vs. 49%, group A vs. B, p value = 0.02, RR = 1.33 (1.1-1.7). Missed abortion and biochemical rates were higher in group B as opposed to group A, 27 vs. 12%, p = 0.01, RR = 0.45(0.24-0.86). When P4 was stratified into five groups based on nanogram per milliliter of progesterone on day 19 (10-15, 15-20, 20-30, 30-40, and >40), there was a trend downward in OPR/LBR (70, 62, 52, 50, and 33%, respectively). There was also an increase in missed abortion/biochemical rates (7, 15, 27, 32, and 20%, respectively). Multiple logistic regression showed an increase in OPR/LBR when accounting for age, day 2 FSH, weight, number of embryos biopsied, and number of euploid embryos. P4 levels >20ng/ml on the day of transfer (during frozen single euploid embryo transfer cycles) were associated with decreased OPR/LBR.

Are all human-derived FSH products the same? A systematic review and meta-analysis using direct and adjusted indirect analyses to deterimine if Fostimon® is more efficient than Metrodin-HP®

OBJECTIVE: Recent randomized trials and systematic reviews have challenged the claim for superiority of recombinant FSH (recFSH) compared with human-derived FSH (hFSH) products. Even so, much of the evidence comes from products that have been removed from the market. If the currently available Fostimon® is superior to the off-market Metrodin-HP®, then data from the latter should not be used to gauge the efficacy of the former. DESIGN: Systematic review and meta-analysis using direct and adjusted indirect evidence synthesis. MATERIALS AND METHODS: Electronic/hand searches (e.g. MEDLINE, EMBASE, CENTRAL) till January 2010 were performed to identify randomized trials (RCTs) comparing Fostimon® vs. Metrodin-HP®, or either hFSH product with recFSH. The primary outcomes were live-birth (LBR), ongoing pregnancy (OPR) and ongoing pregnancy/ live-birth rates (OPR/LBR). The secondary outcomes were clinical pregnancy (CPR), multiple pregnancy (MPR), OHSS and abortion rates, in addition to the cycle demographics. Data was extracted to allow for an intention-to-treat analysis and meta-analyzed using combined direct and adjusted indirect methods. RESULTS: Twenty-two RCTs that met the inclusion criteria were analyzed: Fostimon® vs. Metrodin-HP® (two trials); Fostimon® vs. recFSH (eight trials); Metrodin-HP® vs. recFSH (12 trials). The LBR (OR = 1.72; 95% CI = 1.05 to 2.80), OPR/ LBR, and CPR were all significantly higher favoring Fostimon®. The OPR, MPR, OHSS and miscarriage rates were not significantly different and the cycle demographics were not pooled due to high heterogeneity between the included trials. CONCLUSION: Evidence from RCTs suggests that Fostimon® is superior to Metrodin-HP® in terms of clinical outcomes. Therefore, care should be taken not to assume that all hFSH products have the same efficacy.